Early diagnosis of cystic fibrosis can improve children's growth

EDITOR—Wald and Morris1 seem to have examined carefully our article on the nutritional benefits of neonatal screening in cystic fibrosis2 but they misunderstood some points and failed to grasp the potential advantages of preventing malnutrition in patients with cystic fibrosis.

They comment that our “study design is an ingenious one, but the analysis of the results is problematic.” Ironically, the most ingenious feature is the very element they criticise with their comment that “a difficulty that is not discussed … is that the data in children under 4 years are subject to selection bias.” Selection bias was one of the challenges we overcame in our study design. Our randomisation protocol was designed to include a group that had been screened at birth and a standard diagnosis (control) group.

Once the controls were identified by the unblinding process at 4 years of age, their anthropometric indices of nutritional status since birth were obtained by reviewing records; this information was incorporated into a “what if” analysis—a statistical analysis to determine how the control group would have compared with the screened group if all patients had been identified at birth. Although this was described in the original version of our paper it was deleted during editing but the paper still showed that significant differences persisted.

Wald and Morris ask for “a separate analysis restricted to follow up after the first four years.” We completed the unblinding of controls last April and have accumulated sufficient data to show that significant differences persist. We have shown that if this analysis starts at 4 years of age the proportion of patients with cystic fibrosis who have heights above the 10th centile remains significantly greater in the screened group (P=0.042).

Finally, the comment that “this trial provides no evidence of any benefit of screening” is inappropriate; not only are the nutritional advantages obvious from our study but also the psychological advantages of genetic counselling and the potential pulmonary benefits are evident.3^–5

I strongly disagree with the concern implied by Wald and Morris that “early knowledge of a serious disorder will cause more harm than good if there is no effective remedy.” Our assessment shows that malnutrition can be prevented by neonatal screening. Most doctors caring for patients with cystic fibrosis believe that interventions used to treat the respiratory disease are effective.